This invention relates to pharmaceutical compositions for the intranasal administration of the compound granisetron and its pharmaceutically acceptable salts.
Granisetron (molecular weight 312.4) is 1-methyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1H-indazole-3-carboxamide and has the following structure.

Granisetron is an antagonist of serotonin type 5-HT3 receptors and has anti-emetic activity. It is thought that granisetron acts by binding to receptors in the chemoreceptor trigger zone and, probably, the upper gastrointestinal tract (see pages G86-G90, Therapeutic Drugs, Dollery (ed), 2nd edition, Churchill Livingstone, Edinburgh, (1999)).
Granisetron is typically administered therapeutically as the hydrochloride salt (MW 348.9), but doses are usually expressed in terms of the base (1 mg base is equivalent to 1.12 mg of hydrochloride salt).
For treating nausea and vomiting induced by cytotoxic chemotherapy or radiotherapy, the typical adult oral dose is 1 to 2 mg up to one hour before therapy begins, then 2 mg daily in 1 or 2 divided doses. By intravenous injection, the dose is in the USA 10 μg/kg in both adults and children. For prevention or treatment of postoperative nausea and vomiting in adults, a 1 mg dose is given by intravenous infusion (max. dose 2 mg in one day) (Martindale, The Complete Drug Reference, 33rd Edition, Pharmaceutical Press, pages 1227 and 1228 (2002)).
Both nausea and vomiting impair the absorption of orally administered drugs. It would be advantageous to provide granisetron for administration via a route that avoids the problems associated with oral drug administration. The present invention seeks to address this problem.